The present invention relates to an implantable infusion pump for infusing drugs or other chemicals or solutions into a body wherein the infusion pump is implanted. More particularly, the present invention relates to an implantable infusion pump which compensates for changes in ambient pressure and is largely unaffected by changes in ambient temperature so as to accurately control the flow rate of drugs from the implantable infusion pump into the body.
Infusion pump designs were rarely seen in medical literature until the 1950s. Most of these early infusion pumps were extracorporeal devices of various designs. One such device included a reciprocating air pump driven by an electric motor. Yet another design considered comprised a metal housing for a glass syringe and a compression chamber fed by a tank of nitrogen gas. Yet another such infusion pump included a motorized syringe pump which included an electric motor connected to the worm drive that moved a syringe plunger by a gear box. The gears were interchangeable such that replacement of the gears permitted different delivery rates. Yet another infusion pump included a syringe plunger driven by a rider on a threaded shaft. Numerous other designs were considered for these extracorporeal infusion pumps. P. D. W. Soden in his thesis entitled, "A Methodical Design Study of Miniature Profusion Devices For Chemotherapy of Cancer of the Head and Neck", studied possible designs for producing a miniature profusion device to be carried by ambulating patients receiving chemotherapeutic treatment for cancer of the head and neck. Quoting from his thesis, "Approximately two million alternative design solutions were synthesized and recorded in compact matrix form on a `morphological chart`". One of the numerous design concepts mentioned by Soden for possible use with an extracorporeal infusion pump was the use of a small tubular arrangement containing an elastic metal bellows possibly constructed from preloaded disks so as to form a relatively small diaphragm in the tubular arrangement for exerting a fairly constant force on the drug solution being infused. Due to the size of the diaphragm, this design provided for very little, if any, compensation for changes in atmospheric pressure.
One of the earliest implantable infusion pumps intended for use in laboratory animals comprised a micro-injector comprising a compressed spring held away from a rubber-capped glass tube by a metal alloy disk with a low melting point. Administration of the injection was accomplished by placing the animal near the coils of a high-frequency induction heater. Activation of the coils melted the alloy disk and the spring ejected infusate into the desired site in the animal. A second implantable infusion pump for the continuous infusion of drugs utilized the osmotic pressure developed by a saturated aqueous solution of Congo red dye against water as its power source. The infusion pump comprised a partially collapsed rubber compartment filled with Congo red dye separated from a second water compartment by a semi-permeable cellophane member. Expansion of the rubber compartment as the water moved by osmosis into the Congo red solution ejected the drug from the infusion pump.
Implantable infusion pumps were clinically introduced in 1975. Implantable infusion pumps currently in clinical use or in animal trials anticipating clinical studies in the near future, include vapor pressure powered pumps, peristaltic pumps, and pulsatile solenoid pumps. The vapor pressure powered pump was developed at the University of Minnesota and is described hereafter. The peristaltic pump generally comprises a flexible tube placed in a u-shaped chamber in contact with rollers that press against the tube with sufficient force to occlude the tube's lumen. The rollers are rotated by a motor. As the rotor turns and the rollers compress the lumen of the tube, fluid is moved toward an exit. The rollers and housing are arranged so that a second roller begins to squeeze the tube before the first disengages, preventing backflow of the infusate. Sandia Laboratories, Siemens AG, and Medtronic, Inc. have developed implantable pumps with peristaltic pumping mechanisms. A pulsatile solenoid pump includes a solenoid driven reciprocating chamber with two check valves to move infusate from the reservoir out through the delivery catheter. Infusate is stored in a flexible metal diaphragm reservoir. Such a pump has been developed by Fischell and colleagues at Johns Hopkins University Applied Physics Laboratory and by the Pacesetter Corporation.
These currently available implantable infusion pumps provide drug infusion into the body at rates which are more precisely controllable than can be achieved by conventional oral and bolus injection methods. However, the existing implantable infusion pumps are sensitive to temperature and atmospheric pressure changes such that changes in temperature and atmospheric pressure cause corresponding changes in drug infusion rates from the implantable infusion pumps into the body. With some drugs, particularly those having small therapeutic indices, such changes in drug infusion rates are undesirable and, in certain situations, unacceptable.
One example of an existing implantable infusion pump is described in U.S. Pat. No. 3,731,681, herein incorporated by reference, which describes an implantable infusion pump which uses a liquid/vapor equilibrium to maintain a constant pressure on a drug solution, such as insulin, contained in a drug chamber of the infusion pump in order to maintain a predetermined flow rate of the drug solution from the drug chamber via a capillary tube to an infusion site in the body. In the liquid/vapor powered pump, double chambered design with a rigid outer chamber and a flexible diaphragm separating the chambers is utilized. A liquid/vapor is present in one of the chambers either as a power source or to allow the diaphragm to move without creating a vacuum. However, due to the rigid outer shell structure of the pump, this technique of drug flow control is affected by changes in temperature and atmospheric pressure. Where the patient remains in a local region, the air pressure is a minor variable. However, there are conditions under which both temperature and pressure can change a significant amount. For example, if the patient has a fever, the temperature can change several degrees. The internal pressure change is about 0.5 psi per degree fahrenheit. Assuming an 8 psi driving force at 98.6.degree. F., a twenty-five percent (25%) increase in pressure and drug flow rate can result from a fever of 102.6 degrees fahrenheit. Such changes in flow rate may be unacceptable for certain drugs with small therapeutic indices.
An even more serious situation results from changes in atmospheric pressure. Atmospheric pressure change at any given location on the earth does not significantly affect flow rate of this pump. However, with modern modes of transportation, a patient can rapidly change altitude during travel, such as when traveling in the mountains or when traveling by plane wherein cabin pressures equivalent to five thousand to six thousand feet of altitude are not uncommon. Since the vapor/pressure powered implantable infusion pump of U.S. Pat. No. 3,731,681 is enclosed in a rigid, immovable outer shell structure, it produces a constant internal pressure (at constant temperature) independent of the external pressure. The hydrostatic pressure within the body closely follows the external pressure on the body caused by atmospheric pressure. This is largely due to the compliance of the lungs and the venous circulation. The net effect is a pressure difference across the outflow resistance from the infusion pump (typically a capillary tube or the like) which changes linerally with external pressure. The drug flow rate can increase as much as forty percent (40%) when the patient takes a commercial airline trip.
One method of more accurately controlling the rate of drug delivery is an infusion regulator, such as that disclosed in U.S. Pat. No. 4,299,220. The infusion regulator described therein meters the rate of drug delivery on the basis of the pressure drop across the output or outflow resistance (capillary tube) using a diaphragm valve. An undesirable feature of the infusion regulator is that the drug solution flows through a metering valve at high local shear rates, which may be inappropriate for certain proteinaceous or micellar solutions.
The present invention overcomes these and other problems associated with currently available implantable infusion pumps and infusion regulators.